First trial of spatial and temporal fractionations of the delivered dose using synchrotron microbeam radiation therapy

The technical feasibility of temporal and spatial fractionations of the radiation dose has been evaluated using synchrotron microbeam radiation therapy for brain tumors in rats. A significant increase in lifespan (216%, p < 0.0001) resulted when three fractions of microbeam irradiation were applied to the tumor through three different ports, orthogonal to each other, at 24 h intervals. However, there were no long‐term survivors, and immunohistological studies revealed that 9 L tumors were not entirely ablated.     

X‐Tream quality assurance in synchrotron X‐ray microbeam radiation therapy

Microbeam radiation therapy (MRT) is a novel irradiation technique for brain tumours treatment currently under development at the European Synchrotron Radiation Facility in Grenoble, France. The technique is based on the spatial fractionation of a highly brilliant synchrotron X‐ray beam into an array of microbeams using a multi‐slit collimator (MSC). After promising pre‐clinical results, veterinary trials have recently commenced requiring the need for dedicated quality assurance (QA) procedures. The quality of MRT treatment demands reproducible and precise spatial fractionation of the incoming synchrotron beam. The intensity profile of the microbeams must also be quickly and quantitatively characterized prior to each treatment for comparison with that used for input to the dose‐planning calculations. The Centre for Medical Radiation Physics (University of Wollongong, Australia) has developed an X‐ray treatment monitoring system (X‐Tream) which incorporates a high‐spatial‐resolution silicon strip detector (SSD) specifically designed for MRT. In‐air measurements of the horizontal profile of the intrinsic microbeam X‐ray field in order to determine the relative intensity of each microbeam are presented, and the alignment of the MSC is also assessed. The results show that the SSD is able to resolve individual microbeams which therefore provides invaluable QA of the horizontal field size and microbeam number and shape. They also demonstrate that the SSD used in the X‐Tream system is very sensitive to any small misalignment of the MSC. In order to allow as rapid QA as possible, a fast alignment procedure of the SSD based on X‐ray imaging with a low‐intensity low‐energy beam has been developed and is presented in this publication.     

A new method of creating minibeam patterns for synchrotron radiation therapy: a feasibility study

Several synchrotrons around the world are currently developing innovative radiotherapy techniques with the aim of palliating and possibly curing human brain tumors. Amongst them, microbeam radiation therapy (MRT) and, more recently, minibeam radiation therapy (MBRT) have shown promising results. In MBRT the beam thickness ranges from 500 to 700 µm with a separation between two adjacent minibeams of the same value, whilst in MRT the thickness is of the order of 25–50 µm with a distance between adjacent microbeams of the order of 200 µm. An original method has been developed and tested at the ESRF ID17 biomedical beamline to produce the minibeam patterns. It utilizes a specially developed high‐energy white‐beam chopper whose action is synchronized with the vertical motion of the target moving at constant speed. Each opening of the chopper generates a horizontal beam print. The method described here has the advantage of being simple and reliable, and it allows for an easy control of the patient safety in future clinical trials. To study the feasibility of the method, dosimetric measurements have been performed using Gafchromic HD‐810 films and compared with Monte Carlo simulations. The results of this comparison are discussed.     

Image guidance protocol for synchrotron microbeam radiation therapy

The protocol for image‐guided microbeam radiotherapy (MRT) developed for the Australian Synchrotron's Imaging and Medical Beamline (IMBL) is described. The protocol has been designed for the small‐animal MRT station of IMBL to enable future preclinical trials on rodents. The image guidance procedure allows for low‐dose monochromatic imaging at 50 keV and subsequent semi‐automated sample alignment in 3D with sub‐100 µm accuracy. Following the alignment, a beamline operation mode change is performed and the relevant beamline components are automatically aligned for the treatment (pink) beam to be delivered on the sample. Here, the small‐animal MRT station, the parameters and procedures for the image guidance protocol, as well as the experimental imaging results using phantoms are described. Furthermore, the experimental validation of the protocol using 3D PRESAGE^® dosimeters is reported. It is demonstrated that the sample alignment is maintained after the mode change and the treatment can be delivered within the same spatial accuracy of 100 µm. The results indicate that the proposed approach is viable for preclinical trials of small‐animal MRT.     

Benchmarking and validation of a Geant4–SHADOW Monte Carlo simulation for dose calculations in microbeam radiation therapy

Microbeam radiation therapy (MRT) is a synchrotron‐based radiotherapy modality that uses high‐intensity beams of spatially fractionated radiation to treat tumours. The rapid evolution of MRT towards clinical trials demands accurate treatment planning systems (TPS), as well as independent tools for the verification of TPS calculated dose distributions in order to ensure patient safety and treatment efficacy. Monte Carlo computer simulation represents the most accurate method of dose calculation in patient geometries and is best suited for the purpose of TPS verification. A Monte Carlo model of the ID17 biomedical beamline at the European Synchrotron Radiation Facility has been developed, including recent modifications, using the Geant4 Monte Carlo toolkit interfaced with the SHADOW X‐ray optics and ray‐tracing libraries. The code was benchmarked by simulating dose profiles in water‐equivalent phantoms subject to irradiation by broad‐beam (without spatial fractionation) and microbeam (with spatial fractionation) fields, and comparing against those calculated with a previous model of the beamline developed using the PENELOPE code. Validation against additional experimental dose profiles in water‐equivalent phantoms subject to broad‐beam irradiation was also performed. Good agreement between codes was observed, with the exception of out‐of‐field doses and toward the field edge for larger field sizes. Microbeam results showed good agreement between both codes and experimental results within uncertainties. Results of the experimental validation showed agreement for different beamline configurations. The asymmetry in the out‐of‐field dose profiles due to polarization effects was also investigated, yielding important information for the treatment planning process in MRT. This work represents an important step in the development of a Monte Carlo‐based independent verification tool for treatment planning in MRT.     

Synchrotron X‐ray microbeam dosimetry with a 20 micrometre resolution scintillator fibre‐optic dosimeter

Cancer is one of the leading causes of death worldwide. External beam radiation therapy is one of the most important modalities for the treatment of cancers. Synchrotron microbeam radiation therapy (MRT) is a novel pre‐clinical therapy that uses highly spatially fractionated X‐ray beams to target tumours, allowing doses much higher than conventional radiotherapies to be delivered. A dosimeter with a high spatial resolution is required to provide the appropriate quality assurance for MRT. This work presents a plastic scintillator fibre optic dosimeter with a one‐dimensional spatial resolution of 20 µm, an improvement on the dosimeter with a resolution of 50 µm that was demonstrated in previous work. The ability of this probe to resolve microbeams of width 50 µm has been demonstrated. The major limitations of this method were identified, most notably the low‐light signal resulting from the small sensitive volume, which made valley dose measurements very challenging. A titanium‐based reflective paint was used as a coating on the probe to improve the light collection, but a possible effect of the high‐Z material on the probes water‐equivalence has been identified. The effect of the reflective paint was a 28.5 ± 4.6% increase in the total light collected; it did not affect the shape of the depth‐dose profile, nor did it explain an over‐response observed when used to probe at low depths, when compared with an ionization chamber. With improvements to the data acquisition, this probe design has the potential to provide a water‐equivalent, inexpensive dosimetry tool for MRT.     

Increase of lifespan for glioma‐bearing rats by using minibeam radiation therapy

This feasibility work assesses the therapeutic effectiveness of minibeam radiation therapy, a new synchrotron radiotherapy technique. In this new approach the irradiation is performed on 9L gliosarcoma‐bearing rats with arrays of parallel beams of width 500–700 µm. Two irradiation configurations were compared: a lateral unidirectional irradiation and two orthogonal arrays interlacing at the target. A dose escalation study was performed. A factor of three gain in the mean survival time obtained for some animals paves the way for further exploration of the different possibilities of this technique and its further optimization.     

Comparison of phantom materials for use in quality assurance of microbeam radiation therapy

Microbeam radiation therapy (MRT) is a promising radiotherapy modality that uses arrays of spatially fractionated micrometre‐sized beams of synchrotron radiation to irradiate tumours. Routine dosimetry quality assurance (QA) prior to treatment is necessary to identify any changes in beam condition from the treatment plan, and is undertaken using solid homogeneous phantoms. Solid phantoms are designed for, and routinely used in, megavoltage X‐ray beam radiation therapy. These solid phantoms are not necessarily designed to be water‐equivalent at low X‐ray energies, and therefore may not be suitable for MRT QA. This work quantitatively determines the most appropriate solid phantom to use in dosimetric MRT QA. Simulated dose profiles of various phantom materials were compared with those calculated in water under the same conditions. The phantoms under consideration were RMI457 Solid Water (Gammex‐RMI, Middleton, WI, USA), Plastic Water (CIRS, Norfolk, VA, USA), Plastic Water DT (CIRS, Norfolk, VA, USA), PAGAT (CIRS, Norfolk, VA, USA), RW3 Solid Phantom (PTW Freiburg, Freiburg, Germany), PMMA, Virtual Water (Med‐Cal, Verona, WI, USA) and Perspex. RMI457 Solid Water and Virtual Water were found to be the best approximations for water in MRT dosimetry (within ±3% deviation in peak and 6% in valley). RW3 and Plastic Water DT approximate the relative dose distribution in water (within ±3% deviation in the peak and 5% in the valley). PAGAT, PMMA, Perspex and Plastic Water are not recommended to be used as phantoms for MRT QA, due to dosimetric discrepancies greater than 5%.     

The first microbeam synchrotron X‐ray fluorescence beamline at the Siam Photon Laboratory

The first microbeam synchrotron X‐ray fluorescence (µ‐SXRF) beamline using continuous synchrotron radiation from Siam Photon Source has been constructed and commissioned as of August 2011. Utilizing an X‐ray capillary half‐lens allows synchrotron radiation from a 1.4 T bending magnet of the 1.2 GeV electron storage ring to be focused from a few millimeters‐sized beam to a micrometer‐sized beam. This beamline was originally designed for deep X‐ray lithography (DXL) and was one of the first two operational beamlines at this facility. A modification has been carried out to the beamline in order to additionally enable µ‐SXRF and synchrotron X‐ray powder diffraction (SXPD). Modifications included the installation of a new chamber housing a Si(111) crystal to extract 8 keV synchrotron radiation from the white X‐ray beam (for SXPD), a fixed aperture and three gate valves. Two end‐stations incorporating optics and detectors for µ‐SXRF and SXPD have then been installed immediately upstream of the DXL station, with the three techniques sharing available beam time. The µ‐SXRF station utilizes a polycapillary half‐lens for X‐ray focusing. This optic focuses X‐ray white beam from 5 mm × 2 mm (H × V) at the entrance of the lens down to a diameter of 100 µm FWHM measured at a sample position 22 mm (lens focal point) downstream of the lens exit. The end‐station also incorporates an XYZ motorized sample holder with 25 mm travel per axis, a 5× ZEISS microscope objective with 5 mm × 5 mm field of view coupled to a CCD camera looking to the sample, and an AMPTEK single‐element Si (PIN) solid‐state detector for fluorescence detection. A graphic user interface data acquisition program using the LabVIEW platform has also been developed in‐house to generate a series of single‐column data which are compatible with available XRF data‐processing software. Finally, to test the performance of the µ‐SXRF beamline, an elemental surface profile has been obtained for a piece of ancient pottery from the Ban Chiang archaeological site, a UNESCO heritage site. It was found that the newly constructed µ‐SXRF technique was able to clearly distinguish the distribution of different elements on the specimen.     

Time‐resolved photoelectron spectroscopy using synchrotron radiation time structure

Synchrotron radiation time structure is becoming a common tool for studying dynamic properties of materials. The main limitation is often the wide time domain the user would like to access with pump–probe experiments. In order to perform photoelectron spectroscopy experiments over time scales from milliseconds to picoseconds it is mandatory to measure the time at which each measured photoelectron was created. For this reason the usual CCD camera‐based two‐dimensional detection of electron energy analyzers has been replaced by a new delay‐line detector adapted to the time structure of the SOLEIL synchrotron radiation source. The new two‐dimensional delay‐line detector has a time resolution of 5 ns and was installed on a Scienta SES 2002 electron energy analyzer. The first application has been to characterize the time of flight of the photoemitted electrons as a function of their kinetic energy and the selected pass energy. By repeating the experiment as a function of the available pass energy and of the kinetic energy, a complete characterization of the analyzer behaviour in the time domain has been obtained. Even for kinetic energies as low as 10 eV at 2 eV pass energy, the time spread of the detected electrons is lower than 140 ns. These results and the time structure of the SOLEIL filling modes assure the possibility of performing pump–probe photoelectron spectroscopy experiments with the time resolution given by the SOLEIL pulse width, the best performance of the beamline and of the experimental station.     

Intracerebral delivery of 5‐iodo‐2′‐deoxyuridine in combination with synchrotron stereotactic radiation for the therapy of the F98 glioma

Iodine‐enhanced synchrotron stereotactic radiotherapy takes advantage of the radiation dose‐enhancement produced by high‐Z elements when irradiated with mono‐energetic beams of synchrotron X‐rays. In this study it has been investigated whether therapeutic efficacy could be improved using a thymidine analogue, 5‐iodo‐2′‐deoxyuridine (IUdR), as a radiosentizing agent. IUdR was administered intracerebrally over six days to F98 glioma‐bearing rats using Alzet osmotic pumps, beginning seven days after tumor implantation. On the 14th day, a single 15 Gy dose of 50 keV synchrotron X‐rays was delivered to the brain. Animals were followed until the time of death and the primary endpoints of this study were the mean and median survival times. The median survival times for irradiation alone, chemotherapy alone or their combination were 44, 32 and 46 days, respectively, compared with 24 days for untreated controls. Each treatment alone significantly increased the rats' survival in comparison with the untreated group. Their combination did not, however, significantly improve survival compared with that of X‐irradiation alone or chemotherapy alone. Further studies are required to understand why the combination of chemoradiotherapy was no more effective than X‐irradiation alone.     

Bone‐nanohydroxyapatite spheres interface evaluation by synchrotron radiation X‐ray microfluorescence

Hydroxyapatite (HA) is largely used as bone graft; it seems to be the most promising synthetic implant material, mainly because of its excellent biocompatibility. The crystallinity, particle and pore size of HA are important characteristics and can be modified by decreasing basic structural form below 100 nm and have evoked a great amount of attention for improving prevention, diagnosis, and disease treatment, besides improving bone repair through the biodegradation of the material. The aim of this study was to investigate bone mineral content in bone samples with nanohydroxyapatite and HA spheres, specially its spatial distribution on bone microarchitecture. Circular bone defects were made in both tibiae of 12 White New Zeland adult rabbits (Oryctolagus cuniculus) and were divided randomly into five groups – blood clot (control group), sintered HA, non‐sintered HA, sintered nanoHA and non‐sintered nanoHA – all materials in spherical shape, to smooth handling and accommodation of the surgical bed, and to minimize inflammatory response. The rabbits were euthanatized according to the experimental period of 1 and 4 weeks after surgery. The samples were evaluated by polarized microscopy as well as X‐ray microfluorescence in order to account the bone mineral content bone‐implant interfaces, through synchrotron radiation. Our results revealed greater newly formed bone area in the non‐sintered materials and control groups, and the used technique showed that the amount of calcium of new bone was consistent with both mature bone and HA spheres. In conclusion, the present findings suggest that HA‐based biomaterials are biocompatible, promote osteoconduction and favored bone repair. Copyright © 2011 John Wiley & Sons, Ltd.     

Short‐term effects of synchrotron irradiation on vasculature and tissue in healthy mouse brain

The purpose of this study is to measure the effects of a tomographic synchrotron irradiation on healthy mouse brain. The cerebral cortexes of healthy nude mice were irradiated with a monochromatic synchrotron beam of 79 keV at a dose of 15 Gy in accordance with a protocol of photoactivation of cisplatin previously tested in our laboratory. Forty‐eight hours, one week and one month after irradiation, the blood brain barrier (BBB) permeability was measured in the irradiated area with intravital multiphoton microscopy using fluorescent dyes with molecular weights of 4 and 70 kDa. Vascular parameters and gliosis were also assessed using quantitative immunohistochemistry. No extravasation of the fluorescent dyes was observed in the irradiated area at any measurement time (48 h, 1 week, 1 month). It appears that the BBB remains impermeable to molecules with a molecular weight of 4 kDa and above. The vascular density and vascular surface were unaffected by irradiation and no gliosis was induced. These findings suggest that a 15 Gy/79 keV synchrotron irradiation does not induce important damage on brain vasculature and tissue on the short term following irradiation.     

Quality evaluation of quick‐frozen biological specimens by simultaneous microbeam SAXS/WAXS recordings

The quality of small‐angle X‐ray scattering (SAXS) patterns from quick‐frozen hydrated biological specimens was correlated with the extent of ice crystal formation by simultaneously recording wide‐angle X‐ray scattering (WAXS) of ice, at a micrometer‐order spatial resolution by using X‐ray microbeams. Flight muscle fibers from a giant waterbug, Lethocerus, known to generate well defined small‐angle reflection spots originating from the hexagonal lattices of myofilaments, were quick‐frozen in the presence or absence of various cryoprotectants. Freezing without a cryoprotectant resulted in massive ice‐crystal formation at almost all depths of the specimen, and the occurrence of reflection spots was limited to the region close to the specimen surface. Inclusion of 20% dimethyl sulfoxide or methylpentanediol ensured ideal vitreous ice formation and good diffraction qualities for up to 100 µm from the specimen surface. Glycerol and sucrose were found to be inferior at a 20% concentration, but left the reflection spots observable at depths of up to 100 µm. Thus, the microbeam SAXS/WAXS recording offers a high‐spatial‐resolution means of evaluating the extent of structure preservation of quick‐frozen biological specimens. The technique presented here may also provide useful information in cryoelectron microscopy.     

Elemental and chemical state depth analysis by combined use of a polycapillary and a thin wire in a synchrotron X‐ray microprobe

A simple method is proposed to improve the depth resolution of a conventional X‐ray confocal microscopy system by adding a thin wire close to the sample surface and upstream of the polycapillary in the exit channel. A depth resolution of around 10 μm is easily obtained. The detection efficiency is improved by a factor of two to three times, compared with the thin wire technique previously proposed. It is also shown that not only the elemental distribution but also the X‐ray absorption near‐edge structure (XANES) spectrum from locations below the sample surface can be obtained. Copyright © 2017 John Wiley & Sons, Ltd.     

In vivo high‐resolution synchrotron radiation imaging of collagen‐induced arthritis in a rodent model

In vivo microstructures of the affected feet of collagen‐induced arthritic (CIA) mice were examined using a high‐resolution synchrotron radiation (SR) X‐ray refraction technique with a polychromatic beam issued from a bending magnet. The CIA models were obtained from six‐week‐old DBA/1J mice that were immunized with bovine type II collagen and grouped as grades 0–3 according to a clinical scoring for the severity of arthritis. An X‐ray shadow of a specimen was converted into a visual image on the surface of a CdWO₄ scintillator that was magnified using a microscopic objective lens before being captured with a digital charge‐coupled‐device camera. Various changes in the joint microstructure, including cartilage destruction, periosteal born formation, articular bone thinning and erosion, marrow invasion by pannus progression, and widening joint space, were clearly identified at each level of arthritis severity with an equivalent pixel size of 2.7 µm. These high‐resolution features of destruction in the CIA models have not previously been available from any other conventional imaging modalities except histological light microscopy. However, thickening of the synovial membrane was not resolved in composite images by the SR refraction imaging method. In conclusion, in vivo SR X‐ray microscopic imaging may have potential as a diagnostic tool in small animals that does not require a histochemical preparation stage in examining microstructural changes in joints affected with arthritis. The findings from the SR images are comparable with standard histopathology findings.     

Estimation of soft X‐ray and EUV transition radiation power emitted from the MIRRORCLE‐type tabletop synchrotron

The tabletop synchrotron light sources MIRRORCLE‐6X and MIRRORCLE‐20SX, operating at electron energies E_el = 6 MeV and E_el = 20 MeV, respectively, can emit powerful transition radiation (TR) in the extreme ultraviolet (EUV) and the soft X‐ray regions. To clarify the applicability of these soft X‐ray and EUV sources, the total TR power has been determined. A TR experiment was performed using a 385 nm‐thick Al foil target in MIRRORCLE‐6X. The angular distribution of the emitted power was measured using a detector assembly based on an NE102 scintillator, an optical bundle and a photomultiplier. The maximal measured total TR power for MIRRORCLE‐6X is P_max? 2.95 mW at full power operation. Introduction of an analytical expression for the lifetime of the electron beam allows calculation of the emitted TR power by a tabletop synchrotron light source. Using the above measurement result, and the theoretically determined ratio between the TR power for MIRRORCLE‐6X and MIRRORCLE‐20SX, the total TR power for MIRRORCLE‐20SX can be obtained. The one‐foil TR target thickness is optimized for the 20 MeV electron energy. P_max? 810 mW for MIRRORCLE‐20SX is obtained with a single foil of 240 nm‐thick Be target. The emitted bremsstrahlung is negligible with respect to the emitted TR for optimized TR targets. From a theoretically known TR spectrum it is concluded that MIRRORCLE‐20SX can emit 150 mW of photons with E > 500 eV, which makes it applicable as a source for performing X‐ray lithography. The average wavelength, = 13.6 nm, of the TR emission of MIRRORCLE‐20SX, with a 200 nm Al target, could provide of the order of 1 W EUV.     

Quantitative studies of pyrocarbon‐coated materials using synchrotron radiation

Phase‐contrast imaging provides enhanced image contrast and is important for non‐destructive evaluation of structural materials. In this paper, experimental results on in‐line phase‐contrast imaging using a synchrotron source (ELETTRA, Italy) for objects required in material science applications are discussed. Experiments have been carried out on two types of samples, pyrocarbon‐coated zirconia and pyrocarbon‐coated alumina microspheres. These have applications in both reactor and industrial fields. The phase‐contrast imaging technique is found to be very useful in visualizing and determining the coating thickness of pyrocarbon on zirconia and alumina microspheres. The experiments were carried out at X‐ray energies of 16, 18 and 20 keV and different object‐to‐detector distances. The results describe the contrast values and signal‐to‐noise ratio for both samples. A comprehensive study was carried out to determine the thickness of the pyrocarbon coating on zirconia and alumina microspheres of diameter 500 µm. The advantages of phase‐contrast images are discussed in terms of contrast and resolution, and a comparison is made with absorption images. The results show considerable improvement in contrast with phase‐contrast imaging as compared with absorption radiography.     

The 3D characteristics of post‐traumatic syringomyelia in a rat model: a propagation‐based synchrotron radiation microtomography study

Many published literature sources have described the histopathological characteristics of post‐traumatic syringomyelia (PTS). However, three‐dimensional (3D) visualization studies of PTS have been limited due to the lack of reliable 3D imaging techniques. In this study, the imaging efficiency of propagation‐based synchrotron radiation microtomography (PB‐SRµCT) was determined to detect the 3D morphology of the cavity and surrounding microvasculature network in a rat model of PTS. The rat model of PTS was established using the infinite horizon impactor to produce spinal cord injury (SCI), followed by a subarachnoid injection of kaolin to produce arachnoiditis. PB‐SRµCT imaging and histological examination, as well as fluorescence staining, were conducted on the animals at the tenth week after SCI. The 3D morphology of the cystic cavity was vividly visualized using PB‐SRµCT imaging. The quantitative parameters analyzed by PB‐SRµCT, including the lesion and spared spinal cord tissue area, the minimum and maximum diameters in the cystic cavity, and cavity volume, were largely consistent with the results of the histological assessment. Moreover, the 3D morphology of the cavity and surrounding angioarchitecture could be simultaneously detected on the PB‐SRµCT images. This study demonstrated that high‐resolution PB‐SRµCT could be used for the 3D visualization of trauma‐induced spinal cord cavities and provides valuable quantitative data for cavity characterization. PB‐SRµCT could be used as a reliable imaging technique and offers a novel platform for tracking cavity formation and morphological changes in an experimental animal model of PTS.     

Energy‐dispersive diffraction with synchrotron radiation and a germanium detector

The response of an intrinsic Ge detector in energy‐dispersive diffraction measurements with synchrotron radiation is studied with model calculations and diffraction from perfect Si single‐crystal samples. The high intensity and time‐structure of the synchrotron radiation beam leads to pile‐up of the output pulses, and the energy distribution of the pile‐up pulses is characteristic of the fill pattern of the storage ring. The pile‐up distribution has a single peak and long tail when the interval of the radiation bunches is small, as in the uniform fill pattern, but there are many pile‐up peaks when the bunch distance is a sizable fraction of the length of the shaping amplifier output pulse. A model for the detecting chain response is used to resolve the diffraction spectrum from a perfect Si crystal wafer in the symmetrical Laue case. In the 16‐bunch fill pattern of the ESRF storage ring the spectrum includes a large number of `extra reflections' owing to pile‐up, and the model parameters are refined by a fit to the observed energy spectrum. The model is used to correct for the effects of pile‐up in a measurement with the 1/3 fill pattern of the storage ring. Si reflections (2h,2h,0) are resolved up to h = 7. The pile‐up corrections are very large, but a perfect agreement with the integrated intensities calculated from dynamical diffraction theory is achieved after the corrections. The result also demonstrates the convergence of kinematical and dynamical theories at the limit where the extinction length is much larger than the effective thickness of the perfect crystal. The model is applied to powder diffraction using different fill patterns in simulations of the diffraction pattern, and it is demonstrated that the regularly spaced pile‐up peaks might be misinterpreted to arise from superlattices or phase transitions. The use of energy‐dispersive diffraction in strain mapping in polycrystalline materials is discussed, and it is shown that low count rates but still good statistical accuracy are needed for reliable results.